Sex- and endocrine-stage-differences in middle-aged rats in an animal model of OCD

Various clinical studies suggest that many features of OCD are influenced by sex, age and fluctuations in hormonal levels. Animal models have confirmed these differences, and suggest they are mediated by the serotonergic system. We compared the perseveration behavior in a T-maze after the administration of the 5-HT1A agonist, 8-OH-DPAT (2.0 mg/kg) and the preventive action of subchronic fluoxetine (10 mg/kg, 3 times) in middle-aged (11-14 months) malesand female rats in two endocrine states: irregular cycles (tested in diestrus) or persistent diestrus. After 8-OH-DPAT, females with persistent diestrus presented higher perseveration scores than males and females with irregular cycles. Fluoxetine produced an anticompulsive-like effect only in females with persistent diestrus. Females in persistent diestrus showed higher estradiol levels than those in irregular cycles or males. In all groups 8-OH-DPAT increased ambulation and fluoxetine did not modify this action. In males, the combined administration of fluoxetine and 8-OH-DPAT impaired motor coordination. Data are discussed on the basis of estradiol levels and sex differences.

► In middle-aged rats perseveration induced by 8-OH-DPAT was prevented with fluoxetine. ► 8-OH-DPAT-induced perseveration was higher in females with persistent diestrus. ► Fluoxetine had anticompulsive-like effects only in females with persistent diestrus. ► 8-OH-DPAT increased ambulatory activity. ► Fluoxetine plus 8-OH-DPAT impaired motor coordination.